Julien Mendlewicz

Depression in the community: the first pan-European study DEPRES (Depression Research in European Society).

DEPRES (Depression Research in European Society) is the first large pan-European survey of depression in the community. A total of 13359 of the 78463 adults who participated in screening interviews across six countries were identified as suffering from depression, a 6-month prevalence of 17%. Major depression accounted for 6.9% of the cases of depression and minor depression for 1.8%. Depressed subjects in both these categories perceived that their working or social lives were substantially impaired by depressive symptoms. The remaining 8.3% of depressed subjects considered that their functional impairment was not substantial. A significant proportion of sufferers from depression (43%) failed to seek treatment for their depressive symptoms. Of those who did seek help (57%), most consulted a primary care physician, the frequency of consultation increasing with the severity of depression. Sufferers from major depression imposed the greatest demand on healthcare resources, making almost three times as many visits to their GP or family doctor as non-sufferers (4.4 vs 1.5 visits over 6 months). More than two-thirds of depressed subjects (69%) were not prescribed any treatment and when drug therapy was prescribed (31%), only 25% of these subjects were given antidepressant drugs. The number of days of work lost due to illness increased with the severity of depression. Major depression had most impact on productive work, with sufferers losing four times as many working days over 6 months as non-sufferers. The results of the DEPRES survey confirm the high prevalence of depression in the community and the burden imposed on the individual sufferer in terms of impaired quality of life and on society in terms of healthcare utilization and lost productivity.

Guidelines for depot antipsychotic treatment in schizophrenia

These guidelines for depot antipsychotic treatment in schizophrenia were developed during a two-day consensus conference held on July 29 and 30, 1995 in Siena, Italy. Depot antipsychotic medications were developed in the 1960s as an attempt to improve the long-term treatment of schizophrenia (and potentially other disorders benefiting from long-term antipsychotic medication). Depot drugs as distinguishable from shorter acting intramuscularly administered agents can provide a therapeutic concentration of at least a seven day duration in one parenteral dose. The prevention of relapse in schizophrenia remains an enormous public health challenge worldwide and improvements in this area can have tremendous impact on morbidity, mortality and quality of life, as well as direct and indirect health care costs. Though there has been debate as to what extent depot (long-acting injectable) antipsychotics are associated with significantly fewer relapses and rehospitalizations, in our view when all of the data from individual trials and metaanalyses are taken together, the findings are extremely compelling in favor of depot drugs. However in many countries throughout the world fewer than 20% of individuals with schizophrenia receive these medications. The major advantage of depot antipsychotics over oral medication is facilitation of compliance in medication taking. Non-compliance is very common among patients with schizophrenia and is a frequent cause of relapse. In terms of adverse effects, there are not convincing data that depot drugs are associated with a significantly higher incidence of adverse effects than oral drugs. Therefore in our opinion any patient for whom long-term antipsychotic treatment is indicated should be considered for depot drugs. In choosing which drug the clinician should consider previous experience, personal patient preference, patients history of response (both therapeutic and adverse effects) and pharmacokinetic properties. In conclusion the use of depot antipsychotics has important advantages in facilitating relapse prevention. Certainly pharmacotherapy must be combined with other treatment modalities as needed, but the consistent administration of the former is often what enables the latter.

Treatment resistant depression: methodological overview and operational criteria

A wide variety of definitions are used for Treatment Resistant Depression (TRD), considering various criteria and different concepts. Some of the key issues are: the diagnosis, the treatment adequacy in terms of dose and duration, the treatment response assessment and the number of failed therapeutic trials required. Systematic research has been characterizing the concept and criteria to define the different variables involved. Lack of consensus on these issues limits comparison across clinical trials and interpretation of treatment efficacy in the management of treatment resistant patients. Through reanalyzes of available data, we point out the limits of TRD definitions and propose conceptual and operational criteria for a collaborative research project on TRD. It appears that a number of variables commonly associated to treatment resistance are independent of patients characteristics and mainly refer to misdiagnosis and inadequate treatment. The proposed criteria are intended for therapeutic trials in TRD, combining the evaluation of treatment efficiency and the validation of the concept of TRD itself. Major depression with poor response to two adequate trials of different classes of antidepressants is proposed for an operational definition of TRD. Rationale for this definition is discussed in contrast to alternative definitions.

Frontal and parietal metabolic disturbances in unipolar depression

The authors investigated brain glucose utilization using positron emission tomography (PET) in 12 normal volunteers and 12 unipolar unmedicated depressed patients (six endogenous; six nonendogenous) following injection of [18F]fluoro-deoxyglucose (FDG). Compared by analyses of variance, absolute and relative regional glucose metabolic rates appeared different in depressed patients and control subjects, especially in parietal and frontal lobes. In patients with unipolar depression, metabolic rates were increased in the orbital part of the frontal lobe and decreased in a frontal dorsolateral area. The metabolic supero-basal gradient calculated in the frontal cortex was significantly lower in depressed patients than in normal subjects. Decreased glucose metabolism was also observed in the parietal cortex of depressed patients. No differences in glucose metabolic rates have been detected between endogenous and nonendogenous patients. No correlation has been found between the metabolic data and the Hamilton Rating Scale.

DEPRES II (Depression Research in European Society II) : A patient survey of the symptoms, disability and current management of depression in the community

The first pan-European survey of depression in the community (DEPRES I) demonstrated that 17% of the general population suffer from depression (major depression, minor depression, or depressive symptoms). This article describes findings from a second phase of DEPRES (DEPRES II), in which detailed interviews based on a semi-structured questionnaire (78 questions) were conducted with 1884 DEPRES I participants who had suffered from depression and who consulted a healthcare professional about their symptoms during the previous 6 months. The mean time from onset of depression was 45 months, and the most commonly experienced symptoms during the latest period were low mood (76%), tiredness (73%) and sleep problems (63%). During the previous 6 months, respondents had been unable to undertake normal activities because of their depression for a mean of 30 days, and a mean of 20 days of work had been lost to depression by those in paid employment. Approximately one-third of respondents (30%) had received an antidepressant during the latest period of depression. Significantly more respondents given a selective serotonin reputake inhibitor found that their treatment made them feel more like their normal self than those given a tricyclic antidepressant, and fewer reported treatment-related concentration lapses, weight problems, and heavy-headedness (all P < 0.05). Approximately two-thirds of respondents (70%) had received no antidepressant therapy during the latest period of depression, and prescription of benzodiazepines alone, which are not effective against depression, was widespread (17%). There is a need for education of healthcare professionals to encourage appropriate treatment of depression.

Posttraumatic Stress Disorder: Diagnosis and Epidemiology, Comorbidity and Social Consequences, Biology and Treatment

Epidemiological studies clearly indicate that posttraumatic stress disorder (PTSD) is becoming a major health concern worldwide even if still poorly recognized and not well treated. PTSD commonly co-occurs with other psychiatric disorders, and several symptoms overlap with major depressive disorders, anxiety disorders and substance abuse; this may contribute to diagnostic confusion and underdiagnosis. This anxiety disorder provokes significant occupational, psychiatric, medical and psychosocial disability, and its consequences are enormously costly, not only to the survivors and their families, but also to the health care system and society. Work impairment associated with PTSD is very similar to the amount of work impairment associated with major depression. The pathophysiology of PTSD is multifactorial and involves dysregulation of the serotonergic as well as the noradrenergic system. A rational therapeutic approach should normalize the specific psychobiological alterations associated with PTSD. This can be achieved through the use of antidepressant drugs, mainly of those that potentiate serotonergic mechanisms. Recent double-blind placebo-controlled studies report the efficacy of selective serotonin reuptake inhibitors. Several cognitive-behavioral and psychosocial treatments have also been reported to be efficacious and could be considered when treating PTSD patients.

POLYMORPHIC DNA MARKER ON X CHROMOSOME AND MANIC DEPRESSION

Heredity is an important factor in vulnerability to manic depression. A genetic linkage has been demonstrated between manic depression and coagulation factor IX at Xq27 with a TaqI polymorphism at the F9 locus in DNA samples from peripheral leucocytes of manic depressive probands and relatives in 10 informative families. Statistical analysis of the pedigrees gave a maximum lod score of 3.10 at a recombination fraction of 0.11, demonstrating a linkage between a manic depressive locus and the F9 locus in the Xq27 region.

BRAIN GLUCOSE METABOLISM IN BORDERLINE PERSONALITY DISORDER

We searched for regional cerebral metabolic disturbances in patients with borderline personality disorder (BPD). Ten inpatients with BPD, no current DSM-IIIR Axis I diagnosis and free of any psychotropic substances, were compared with 15 age-matched control subjects using positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose and semiquantitative analysis of regional glucose metabolic activity. We found relative hypometabolism in patients with borderline personality disorder at the level of the premotor and prefrontal cortical areas, the anterior part of the cingulate cortex and the thalamic, caudate and lenticular nuclei. This study shows significant cerebral metabolic disturbances in patients with borderline personality disorder. These metabolic disturbances, which are similar to some of those described in other psychiatric entities, may help to understand the characteristic clinical aspects of this disorder.

Sex difference in 5HT2 receptor in the living human brain

Serotonergic mechanisms are involved in gender-related behaviors and psychiatric conditions like aggression, eating disorders, depression, impulsivity or suicide. We studied gender differences in the living human brain type-2 serotonin receptor (5HT2r). Twenty-two healthy age-matched men and women were investigated using positron emission tomography and the selective radiotracer, 18F-labeled altanserin. Binding was quantified using a non-linear least-squares minimization procedure. We found significantly higher 5HT2r binding capacity in men than in women, especially in the frontal and cingulate cortices. Distinct liability for men and women to suffer from some psychiatric disorders responding to serotonergic agents may be related to differences in brain serotonin receptors.

Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study.

Based on our preclinical data showing a potential accelerating effect of acetylsalicylic acid (ASA) in combination with fluoxetine in an animal model of depression, we examined the effect of ASA augmentation therapy on selective reuptake inhibitors (SSRI) in major depressed non-responder patients. Twenty-four non-responder patients having received at least 4 weeks of an adequate SSRI treatment were included in a pilot open-label study. Participants were treated openly during 4 weeks with 160 mg/day ASA in addition to their current antidepressant treatment. The combination SSRI–ASA was associated with a response rate of 52.4%. Remission was achieved in 43% of the total sample and 82% of the responder sample. In the responder group, a significant improvement was observed within week 1 (mean Hamilton Depression Rating Scale-21 items at day 0=29.3±4.5, at day 7=14.0±4.1; P<0.0001) and remained sustained until day 28. Despite limitations due to the open nature of this study, our preliminary results confirm our preclinical findings and are in favour of an accelerating effect of ASA in combination with SSRIs in the treatment of major depression. Potential physiological and biochemical mechanisms may involve an anti-inflammatory and/or neurotrophic effect.